DATA EXTRACTION: One investigator extracted data with review by a second investigator. Investigators independently assessed the risk of bias and strength of evidence (SOE) (ie, confidence in the estimate of effects).

RESULTS: Nineteen randomized controlled trials (RCTs), 4 with a low risk of bias, evaluated supplements or variations of the gluten/casein-free diet and other dietary approaches. Populations, interventions, and outcomes varied. Ω-3 supplementation did not affect challenging behaviors and was associated with minimal harms (low SOE). Two RCTs of different digestive enzymes reported mixed effects on symptom severity (insufficient SOE). Studies of other supplements (methyl B12, levocarnitine) reported some improvements in symptom severity (insufficient SOE). Studies evaluating gluten/casein-free diets reported some parent-rated improvements in communication and challenging behaviors; however, data were inadequate to make conclusions about the body of evidence (insufficient SOE). Studies of gluten- or casein-containing challenge foods reported no effects on behavior or gastrointestinal symptoms with challenge foods (insufficient SOE); 1 RCT reported no effects of camel’s milk on ASD severity (insufficient SOE). Harms were disparate.

LIMITATIONS: Studies were small and short-term, and there were few fully categorized populations or concomitant interventions.

CONCLUSIONS: There is little evidence to support the use of nutritional supplements or dietary therapies for children with ASD.

There has been a lot of concern that abnormal GI function contributes to both behavioral and gastrointestinal symptoms in children with autism. To categorize some of these problems, the term ‘leaky gut’ has been used.

According to the authors, all of the study subjects underwent endoscopy and “all hadclinical indicationsfor diagnostic endoscopy.” Most common indications were parental reports of abdominal pain and diarrhea.

Key findings:

Disaccharidase activity levels were not significantly different between the groups. In agreement with prior studies, there was frequent lactase deficiency, with 66% of ASD children in this study with deficient enzyme activity (<15 μmol/min/g). However, lactase activity in the children with ASD was not lower than the non-ASD children.

There were no significant differences in measures of intestinal permeability. Normative values for lactulose and rhamnose ratio are not definitively established. However, when using similar cutoff ratios, there were similar results in both groups.

Calprotectin:

Intestinal inflammatory markers (calprotectin/lactoferrin) were not significantly different, after the authors excluded the five “neurotypical” children who were diagnosed with inflammatory bowel disease.

For calprotectin, the authors considered a level <50 mcg/g to be normal. In the ASD group, 31of 49 (63%) had abnormal calprotectin compared with 19 of 31 (61%) in the non-ASD group.

For calprotectin levels >150 mcg/g, 9 of 49 (18%) reached this level in the ASD group and 8 of 31 (26%) in the non-ASD group.

Histology:

Similar levels of GI tract inflammation were noted in both groups –generally mild.

In the ASD group, 32 (52%) had inflammation somewhere in their GI tract, “but it was generally mild and non-diagnostic.” In the ASD group, five had features consistent with GERD, two had eosinophilic esophagitis (EoE). There were 12 (19%) who had colonic inflammation and 3 (5%) with ileal inflammation. None had celiac disease or H pylori.

In the non-ASD group, four had EoE, four (8%) had ileal inflammation, and nine (18%) had colonic inflammation. The authors noted Crohn’s disease in three and a total of five children with IBD.

My take:

This study suggests that symptomatic children with autism have similar (and probably not worse) GI problems as neurotypical children. The idea that children with autism have a more leaky gut than children without autism is quite dubious based on these results.

The biggest problem for GI physicians is not addressed in this study and involves children with and without autism:appropriate selection for evaluation. While the authors chose children with “clinical indications,” these, in fact, are often subjective and with permissive interpretation could be used to justify endoscopy in 40% of children.

Another huge problem is interpretation of abnormal results. While the authors report large numbers with intestinal inflammation in both groups, most of this was considered to be insignificant clinically. How should trivial inflammation be reported in studies? This problem is not unique to this study and makes it difficult to assess the value of endoscopy more broadly.

A few useful studies provide reassurances regarding exposures in the prenatal period and perinatal period that we should NOT worry about.

CN Bernstein et al. Clin Gastroenterol Hepatol 2016; 14: 50-7.

In this study with 1671 individuals with inflammatory bowel disease and 10,488 controls, “people with IBD were not more likely to have been born by cesarean section than controls or siblings without IBD. These findings indicate that events of the immediate postpartum period that shape the developing intestinal microbiome do not affect risk for IBD.”

For parents of autistic kids who avoid fish, this article provides information indicating that this is counter-productive. ” Seafood consumption during pregnancy is thought to be beneficial for child neuropsychological development, but to our knowledge no large cohort studies with high fatty fish consumption have analyzed the association by seafood subtype.” The authors “evaluated 1,892 and 1,589 mother-child pairs at the ages of 14 months and 5 years, respectively, in a population-based Spanish birth cohort established during 2004–2008…” Key finding: “Consumption of large fatty fish during pregnancy presents moderate child neuropsychological benefits, including improvements in cognitive functioning and some protection from autism-spectrum traits.”

My take: We often worry about the wrong things. These articles provide reassurance that mode of birth and consumption of seafood during pregnancy are things we should not worry about.

Wednesday’s well publicized debate unfortunately discussed vaccination. Perhaps it is not surprising that a businessman/entertainer, Donald Trump, reiterated misinformation. Yet, the two former physicians (Ben Carson and Rand Paul) on the stage also provided misleading information. A good write-up of this issue from the NY Times: Not Up for Debate: The Science Behind Vaccination

Here’s an excerpt:

Here are the facts:

Vaccines aren’t linked to autism.

The number of vaccines children receive is not more concerning than it used to be.

Delaying their administration provides no benefit, while leaving children at risk.

All the childhood vaccines are important.

There is no evidence that links vaccines to autism. Many, many, many studies have confirmed this. The most recent Cochrane systematic review of research on the MMR vaccine included six self-controlled case series studies, two ecological studies, one case crossover trial, five time series trials, 17 case-control studies, 27 cohort studies and five randomized controlled trials. More than 15 million children took part in this research. No one could find evidence that vaccines are associated with autism….

It’s also not correct to call autism an “epidemic,” as Mr. Trump often seems to do. Autism is more prevalent as a diagnosis than it used to be. But much of that in recent years is because we’ve changed the definition of what it means to have “autism spectrum disorder.” For instance, 10 years ago, two-thirds of children diagnosed with autism had below-average intelligence. But today only about a third of those diagnosed with A.S.D. do. The fastest-growing group of children with autism have average or above average intelligence. We’re being more inclusive in the diagnosis…

Mr. Carson, though observing there was no evidence linking vaccines to autism, also said that many pediatricians were recognizing that “we are probably giving way too many in too short a period of time.” I know of no data that supports this assertion. Pediatricians, as a group, overwhelmingly support vaccines and the current vaccine schedule…

Spacing out vaccines provides no benefit, and leaves children susceptible to illnesses for a longer time…

Today, the number of antigens contained in all the vaccines given to a child by age 2 is less than 315. In contrast, it’s thought a child most likely fights off 2,000 to 6,000 antigens every day from the environment.

An unrelated commentary, “Social Distancing and the Unvaccinated,” (NEJM 2015; 372: 1481-83) notes that a recent ruling (Phillips v City of New York) upholds the state’s authority to bar unvaccinated children from school during outbreaks. This practice is referred to as social distancing to lessen likelihood of further transmission. This “reiterated the Supreme Court decision in the 1905 case Jacobson v. Massachusetts, which clearly found vaccine mandates constitutional.”

GI Care For Kids: Our group has been very supportive of the Crohn’s and Colitis Foundation of America (CCFA) and especially active in staffing the yearly Camp Oasis for more than 20 years. Throughout the year, there are a number of other events to support CCFA. This past weekend many of us participated in “Taking Steps.” Here are a few pictures:

Dr. Spandorfer’s team raised a great deal of money (50K) and he/his family were featured in the Atlanta Journal Constitution (Local Family Takes Big Steps to Raise Awareness). His son, Jack, spoke at the event, and was honored as this year’s hero. They also had pretty clever T-shirts

A recent NY Times editorial by the lead author of a provocative study in Pediatrics (Published online March 3, 2014 (doi: 10.1542/peds.2013-2365) argues that educational efforts to inform parents may not improve vaccination rates in children.

“we found that parents with mixed or negative feelings toward vaccines actually became less likely to say they would vaccinate a future child after receiving information debunking the myth that vaccines cause autism.

Surprising as this may seem, our finding is consistent with a great deal of research on how people react to their beliefs being challenged. People frequently resist information that contradicts their views, such as corrective information— for example, by bringing to mind reasons to maintain their belief — and in some cases actually end up believing it more strongly as a result….

A more promising approach would require parents to consult with their health care provider, as the Oregon law also allows them to do. Parents name their children’s doctor as their most trusted source of vaccine information. That trust might allow doctors to do what evidence alone cannot: persuade parents to protect their children as well as yours and mine.